Cerebral edema occurs after many types of injury. Its occurrence, especially after ischemia or hypoxia can lead to further deterioration and perhaps death. Successful treatment or control of edema may improve outcome. Since ischemic and hypoxic accidents often occur in middle-aged people, improvement of outcome would hopefully increase the productive life of these individuals. An understanding of the basic pathophysiology of cerebral edema may lead to better understanding and control of several diseases. The proposed project will examine the relationship and interaction of various components that affect edema formation in animals. A better understanding of edema formation during controlled assaults in animals should lead to better conceptualization and treatment of this problem in man. Specifically, both cellular (neuronal and glial) and vascular factor appear to play major roles in the production of cerebral edema. In certain experimental situations the vascular factors have been studied by directly injuring the cerebral vessels. Experimental analysis of the cellular factors is less successful. The reason for this the applicant believes rests with the experimental models used, as most of these are model of cerebral ischemia. These models, by definition, involve both a cellular and vascular insult. The proposed study plans to develop a hypoxic models of cerebral edema. The continued perfusion during this insult period reduces the large changes in perfusion pressure seen during ischemia. The experiments will be done in rats, using the modified Levinei model of unilateral carotid ligation, hypoxia, and controlled ventilation. The relationship of edema formation to neuronal energy failure, osmotic pressure, and electrolyte shifts will be studied. Changes in perfusion pressure, both increased and decreased, will be super imposed to examine its relationship to hypoxia mediated edema formation. These experiments will help clarify the role of oxygen lack in edema formation, and help delineate cellular changes that may be contributing to the formation of edema. These studies have relevance to neurology, anesthesiology, and intensive care in that better understanding of these basic processes may lead to better clinical treatment of certain patients.